摘要
目的探讨MET基因单核苷酸多态性(SNP)与肝细胞癌术后患者总生存期(OS)的关联。方法选取广西医科大学附属肿瘤医院2004-06-01-2013-12-31接受肝细胞癌根治术治疗的336例患者为研究对象,使用Sequenom Mass Array法对MET基因的4个SNP位点(rs121 A>G、rs38840 C>T、rs41739 A>G和rs6566 A>G)进行基因分型并利用乘积极限法(Kaplan-Meier)和Cox比例风险回归模型分析SNP位点基因型与肝细胞癌术后患者OS关系。结果饮酒(HR=1.36,95%CI为1.02~1.82,P=0.035)、吸烟(HR=1.33,95%CI为1.02~1.75,P=0.038)、巴塞罗那分期(HR=2.89,95%CI为2.22~3.76,P<0.001)、肿瘤直径(HR=1.77,95%CI为1.35~2.32,P<0.001)、是否发生癌栓(HR=2.15,95%CI为1.62~2.85,P<0.001)和高血压(HR=0.51,95%CI为0.28~0.94,P=0.031)均与肝细胞癌术后患者OS有统计学意义的关联,在单个SNP位点分析时,MET基因各SNP位点与肝细胞癌术后患者OS均无统计学意义的关联,均P>0.05。进一步分析SNP-SNP之间的联合作用,发现携带2~4个潜在风险基因型(简称风险基因型:rs1621 AA、rs38840 CT/TT、rs41739 AA和rs6566 AA)的肝细胞癌术后患者比携带0~1个风险基因型患者的中位生存时间(MST)缩短,差异有统计学意义,MST分别为25.83和30.29个月,P=0.017。Cox比例风险回归分析发现,携带2~4个风险基因型肝细胞癌术后患者发生死亡的风险是携带0~1个风险基因型患者的1.33倍,HR=1.33,95%CI为1.03~1.73,P=0.032,是肝细胞癌术后患者预后的独立危险因素。结论MET基因多态位点rs1621、rs38840、rs41739和rs6566的联合作用可能影响肝细胞癌术后患者的生存结局,其风险基因型的联合作用使肝细胞癌术后患者MST缩短。
Objective To explore the relationship between single nucleotide polymorphism(SNP)individually and jointly and overall survival(OS)of patients with hepatocellular carcinoma(HCC)after operation.Methods A total of 336 HCC patients with undergone radical surgery resection in the Guangxi Medical University Cancer Hospital from June 1,2004 to December 31,2013 were included in his study.Four candidate SNPs(rs1621 A>G),rs38840 C>T,rs41739 A>G and rs6566 A>G in MET were genotyped by Sequenom Mass Array,and used Kaplan-Meier analysis and Cox proportional hazards regression model to evaluate the effect of genotypes and OS.Results Drinking(HR=1.36,95%CI:1.02-1.82,P=0.035),smoking(HR=1.33,95%CI:1.02-1.75,P=0.038),BCLC staging(HR=2.89,95%CI:2.22-3.76,P<0.001),tumor diameter(HR=1.77,95%CI:1.35-2.32,P<0.001),cancer thrombus(HR=2.15,95%CI:1.62-2.85,P<0.001)and hypertension(HR=0.51,95%CI:0.28-0.94,P=0.031)were statistically correlated with OS in patients after hepatocellular carcinoma surgery.Based on the analysis of individual SNPs,no significant relation was found between these SNPs and the OS of HCC patients.Kaplan-Meier analysis showed a significantly shorter OS in patients with 2-4 risk genotypes than those with 0-1 risk genotypes(MST=25.83 months vs 30.29 months,P=0.017).Cox proportional hazard regression analysis found that patients with 2 to 4 risk genotypes were 1.33 times more likely to die after surgery for patients with 0 to 1 risk genotypes(HR=1.33,95%CI:1.03-1.73,P=0.032),it was an independent risk factor for the prognosis of patients with hepatocellular carcinoma after surgery.Conclusions Our results indicated that MET SNPs(rs1621 AA,rs38840 CT/TT,rs41739 AA and rs6566 AA)jointly affect the overall survival time of patients with HCC after operation,which may serve as an independent prognostic marker for patients with HCC after operation.
作者
林秋伶
邱模勤
周子寒
蒋燕霁
梁秀妹
刘颖春
周先果
余红平
LIN Qiu-ling;QIU Mo-qin;ZHOU Zi-han;JIANG Yan-ji;LIANG Xiu-mei;LIU Ying-chun;ZHOU Xian-guo;YU Hong-ping(Guangxi Medical University Cancer Hospital,Nanning 5300211,China;Department of Epidemiology and Biostatistics,School of Public Health,Guangxi Medical University,Nanning 530021,China;Guangxi Cancer Center Guangxi Office for Cancer Prevention and Control,Nanning 530021,China)
出处
《中华肿瘤防治杂志》
CAS
北大核心
2021年第7期526-531,共6页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(81660567,81460516)
广西重点研发计划(AB18050020,AA18221001)
广西自然科学基金重点项目(2018GXNS-FDA050012)。
关键词
肝细胞癌
预后
MET基因
单核苷酸多态性
hepatocellular carcinoma
prognosis
MET gene
single nucleotide polymorphism